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Acute Lymphocytic LeukemiaPhase 2NCT02043587

Chemotherapy With Liposomal Cytarabine CNS Prophylaxis for Adult Acute Lymphoblastic Leukemia & Lymphoblastic Lymphoma

A Phase 2 study testing DNR, VCR and PEG-asp in people with Acute Lymphocytic Leukemia and Adult Lymphoblastic Lymphoma, run by University of California, San Diego at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The objective of this protocol is to improve survival for adults with acute lymphoblastic leukemia or acute lymphoblastic lymphoma by reducing systemic and central nervous system (CNS) relapse with acceptable toxicity using intensive chemotherapy with liposomal cytarabine (Depocyt®) CNS prophylaxis. Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
DNR, VCR and PEG-asp
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
4 sitesUnited States
Study dates
Jan 2014to 14 Apr 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Ability to understand and the willingness to sign a written informed consent.
  • Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma as defined by the World Health Organization [94]
  • Untreated disease EXCEPT for corticosteroids, hydroxyurea, leukapheresis, and/or tyrosine kinase inhibitors for up to 2 weeks prior to initiation of study therapy.
  • Age 18 through 60 years
  • ECOG performance status 0,1, or 2 (see Appendix A)
  • Adequate organ function defined as:
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  • Total bilirubin < 2 mg/dL (unless due to ALL)
  • AST(SGOT)/ALT(SGPT) < 3 times institutional upper limit of normal (unless due to ALL)
  • Serum creatinine < 2 mg/dL (unless elevated creatinine felt by investigator to be acute and reversible) OR creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Left ventricular ejection fraction ≥50%
  • Women of child-bearing potential and men with partners of child- bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Who cannot join

  • Current or anticipated use of other investigational agents during the study
  • Known central nervous system mass lesion
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to liposomal cytarabine or other agents used in study inclusive of known allergy to polyethylene glycol.
  • History of unprovoked venous thrombosis/thromboembolism
  • Recurrent or chronic pancreatitis
  • Uncontrolled diabetes mellitus
Show all 10Show fewer
  • Uncontrolled intercurrent illness that would limit compliance with study requirements including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or nursing.
  • Any condition, in the opinion of the investigator, that compromises compliance with study requirements
  • Known HIV positivity

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • UCSD, Division of Blood and Marrow Transplantation, Moores Cancer Center

    La Jolla, California, 92093

  • Hematological Malignancies/Stem Cell Transplantation Unit, David Geffen School of Medicine at UCLA

    Los Angeles, California, 90095

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • UCSF Comprehensive Cancer Center

    San Francisco, California, 94143-0324

Other trials in United States

About this study

Official title: A Phase II Study of Punctual, Cyclic, and Intensive Chemotherapy With Liposomal Cytarabine (Depocyt®) CNS Prophylaxis for Adults With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

The objective of this protocol is to improve survival for adults with acute lymphoblastic leukemia or acute lymphoblastic lymphoma by reducing systemic and central nervous system (CNS) relapse with acceptable toxicity using intensive chemotherapy with liposomal cytarabine (Depocyt®) CNS prophylaxis.

Read the detailed description

This treatment regimen builds on the "Linker" regimen/UCSF Protocol 8707 ALL regimen backbone with the goal of improved efficacy and acceptable toxicity by substituting pegylated asparaginase for native L-asparaginase, the addition of rituximab for pre-B-cell ALL, and the addition of dasatinib for Philadelphia chromosome/BCR-ABL positive ALL, and the addition of cyclophosphamide for younger adults. In addition, the study regimen aims to reduce CNS relapse through the use of intrathecal liposomal cytarabine in place of intrathecal methotrexate for CNS relapse prophylaxis and

The regimen uses 3 modules of therapy with non-cross-resistant chemotherapy agents. Rituximab is added for a total of 8 doses for patients with pre-B-cell ALL. Dasatinib is added for patients with Ph+ ALL.

Course 1A (Induction): Daunorubicin, vincristine, PEG-asparaginase, and prednisone for all patients with the addition of cyclophosphamide for patients 18-39 years of age. Treatment is intensified for patients with disease present on a day 14 bone marrow biopsies during Induction Course 1A. In addition to standard analyses, minimal residual disease will be assessed on day 14 and remission bone marrow aspirates and correlated with outcomes.

Course 1B: High-dose methotrexate, oral 6-mercaptopurine, and PEG-asparaginase.

Course 1C: High-dose cytarabine and etoposide.

The 3 courses then repeat (2A (Intensification), 2B, 2C) followed by a final "B" cycle (3B) of high-dose methotrexate, 6-mercaptopurine, and PEG-asparaginase.

After completion of Course 3B, patients proceed to maintenance chemotherapy with monthly methotrexate, vincristine, 6-mercaptopurine, and prednisone cycles for 24 months with a single dose PEG-asparaginase given in month 1 of Maintenance.

CNS prophylaxis: Intrathecal liposomal cytarabine replaces intrathecal methotrexate CNS prophylaxis and is given every 2 weeks during the "A" Induction and Intensification courses then every 3 months during Maintenance for a total of 8 doses. Given the presence of CNS penetrating chemotherapy in the "B" and "C" cycles, intrathecal liposomal cytarabine is not given due to risk of excessive CNS toxicity.

There is a randomization to hydrocortisone or placebo premedication prior to PEG-asparaginase.

Being tested
DNR, VCR, PEG-asp, CTX, Prednisone
Keywords
Acute lymphoblastic leukemia, Lymphoblastic leukemia, Lymphoblastic lymphoma
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DNRDrug

    Also called Daunorubicin, Daunorubicin Hydrochloride, Cerubidine, Daunomycin

    Daunorubicin 60 mg/m2 IV (in the vein) daily 1,2,3 Courses 1A, 2A

  • VCRDrug

    Also called Vincristine, Oncovin, Vincasar, PFS

    1.4 mg/m2 IV, days 1, 8, 15, 22 (cap at 2mg for ages >50) during Courses 1A, 2A; Maintenance: Day 1 during months 2-12

  • PEG-aspDrug

    Also called PEG-L-asparaginase, Oncaspar, PEG-asparaginase, pegasparagase

    2,000 IU/m2 IV for ages </= 50, age > 50, 1000 IU/m2 IV Day 16, Courses 1A \& 2A; Day 18, Course 1B; Day 17, Course 2B; Day 16, Maintenance, Month 1

  • CTXDrug

    Also called Cyclophosphamide, Cytoxan, Endoxan, Neosar

    750 mg/m2 IV, days 1 \&15 for subjects <40 year of age, substitute cyclophosphamide 500 mg/m2 IV over 60 minutes every 12 hours for 4 doses on days 15 \& 16 for subjects < 40 years of age if day 14 bone marrow M2 or M3; Courses 1A \& 2A

  • PrednisoneDrug

    Also called Deltasone

    60 mg/m2 orally once daily on days 1-28 during Courses 1A \& 2A; Maintenance: Monthly, days 1-5

  • Liposomal AraCDrug

    Also called Liposomal cytarabine, DepoCyt

    25 mg intrathecal (IT), on days 1 \& 15 during Courses 1A \& 2A; 50 mg intrathecal on day 1 during Maintenance Months 1 through 4

  • MTXDrug

    Also called Methotrexate, Rheumatrex, Trexall

    220 mg/m2 IV bolus over 15 minutes then 60 mg/m2/hour for 36 hours once on days 2-3 and 16-17 during Courses 1B \& 2B; 20 mg/m2 orally one day per week every 7 days during Maintenance Months

  • LCVDrug

    Also called Leucovorin

    50 mg/m2 IV over 15-30 minutes every 6 hours for 3 doses to begin immediately after completion of methotrexate infusion, then 10 mg/m2 orally or IV over 15-30 minutes every 6 hours until methotrexate level less than 0.1 micromolar during Courses 1B \& 2B

  • AraCDrug

    Also called Cytarabine, Ara-C, Arabinosylcytosine, Cytosar-U

    2,000 mg/m2 IV, days 1-4 during Courses 1C \& 2C

  • EtoposideDrug

    Also called VP-16, VePesid, Toposar

    500 mg/m2 IV over 3 hours once daily on days 1-4 during Courses 1C \& 2C

  • DasatinibDrug

    Also called Sprycel

    140 mg orally daily if BCR/ABL positive and/or Ph+

  • RituximabDrug

    Also called Rituxan

    375 mg/m2 IV once daily on days 1 \& 15 (precursor B-cell ALL only, administer per institutional protocol) during Courses 1A, 1B, 1C \& 2A

  • HydrocortisoneDrug

    Also called Hydrocortisone sodium succinate, Solu-Cortef

    Randomize patients proceeding to Course 1B to hydrocortisone versus placebo prior to PEG-asparaginase treatments in Courses 1B, 2B, 3B, and Maintenance month 1

Study groups in NCT02043587
Study groupRoleWhat they receive
Chemotherapy for ALLExperimentalCourse 1A: DNR 60 mg/m2 IV d1,2,3; VCR 1.4 mg/m2 d1,8,15,22 (cap 2 mg age >50); PEG-asp 2000 IU/m2 IV d16, age >50 1000 IU/m2, cap 3750 IU/m2; CTX 750 mg/m2 d1,15 age < 40; Prednisone 60 mg/m2 PO d1-28; Liposomal AraC 25 mg IT d1, 15 1B: MTX 220 mg/m2 IV then 60 mg/m2/h for 36h d2-3,d16-17; LCV 50 mg/m2 IV q6h x3 then 10 mg/m2 PO/IV q6h til MTX <0.1 uM; 6-MP 60 mg/m2 PO d2-8, d16-22; PEG-asp 2000 IU/m2 IV d18, age >50 1000 IU/m2, cap 3750 IU/m2 1C: AraC 2 g/m2 IV d1-4; Etoposide 500 mg/m2 IV d1-4 1A-C repeat x1(2A-C) then 3rd Course B (3B) Maintenance (monthly, 24 mo): Prednisone 60 mg/m2 PO d1-5; VCR 1.4 mg/m2 IV d1 (cap 2 mg age >50); MTX 20 mg/m2 PO wkly; 6-MP 60 mg/m2 PO qd PEG-asp 2000 IU/m2 IV d16, age >50 1000 IU/m2, cap 3,750 IU/m2 (Mo. 1) Maintenance mo. 1-4: Liposomal AraC 50 mg IT d1 Dasatinib 140 mg PO qd if Ph/BCR-ABL+; Rituximab 375 mg/m2 IV d1,15 of 1A-C, 2A (Pre-B) 1:1 randomization: hydrocortisone v. placebo before PEG-asp 1B, 2B, \& Maint.
Receives: Drug: DNR; Drug: VCR; Drug: PEG-asp; Drug: CTX; Drug: Prednisone; Drug: Liposomal AraC; Drug: MTX; Drug: LCV; Drug: AraC; Drug: Etoposide; Drug: Dasatinib; Drug: Rituximab; Drug: Hydrocortisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival

    Measured: 3-year

Secondary outcomes (8)

  1. Liposomal cytarabine toxicity

    Measured: 3 years

  2. CNS relapse rate

    Measured: 3-year

  3. Overall survival

    Measured: 3-year

  4. Leukemia-free survival

    Measured: 3-year

  5. Efficacy of hydrocortisone premedication for reduced PEG-asparaginase allergic reactions

    Measured: 3 years

  6. PEG-asparaginase toxicities

    Measured: 3 years

  7. Complete and overall response rates

    Measured: 3 years

  8. Non-relapse mortality

    Measured: 3-year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2014 (estimated)
  2. Study startJan 2014
  3. Primary completion14 Apr 2022
  4. Study completion14 Apr 2022

Why it stopped: Original investigator for the trial has left

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02043587
Sponsor's protocol ID
130934
Status last verified
Apr 2022
First submitted
21 Jan 2014
Last updated
2 May 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Linker C, Damon L, Ries C, Navarro W. Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia. J Clin Oncol. 2002 May 15;20(10):2464-71. doi: 10.1200/JCO.2002.07.116.

    PubMed 12011123

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DNR, VCR and PEG-asp in people with Acute Lymphocytic Leukemia and Adult Lymphoblastic Lymphoma, run by University of California, San Diego at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Original investigator for the trial has left). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (time frame: 3-year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02043587, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2022.

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